The goal of this project for the coming year is to continue our studies of the mechanisms underlying the responses of the central nervous system (CNS) to injury and the basis for the partial recovery that can occur with time. Animal models of CNS lesions affecting adult humans will be created in mature animals with ablations of the cerebral cortex and with kainic acid and 6-hydroxydopamine induced lesions of the basal ganglia and thalamus. Animal models of CNS injury affecting immature humans will be produced in neonatal animals with ablations of the cerebral cortex and with cerebral lesions induced by hypoxic-ischemic insults. A central focus concerns the immediate and long-term responses to injury of CNS neurotransmitter receptor systems including glutamate, Gamma-aminobutyric acid/benzodiazepine, opiates, dopamine, and acetylcholine. Investigations will be performed using awake behaving animals, tissue from basal ganglia, thalamus, brainstem and spinal cord, and neuronal cell cultures. The experimental approaches include recordings of single neuronal unit activity, studies of neurotransmitter receptors, determinations of glucose metabolic activity, and investigation of ionic conductances in mammalian nerve cell membranes.